Sex hormone-binding globulin is synthesized in target cells

Sex steroid hormones influence prostate development and maintenance through their roles in prostate cellular proliferation, differentiation and apoptosis. Although suspected to be involved in prostate carcinogenesis, an association between circulating androgens and prostate cancer has not been clearly established in epidemiologic studies. We conducted a nested case-control study with prospectively collected samples in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, to examine associations of prostate cancer with androstenedione (D4-A), testosterone (T), sex hormone-binding globulin (SHBG) and 3a-androstanediol glucuronide (3a-diolG). A total of 727 incident Caucasian prostate cancer cases (age ≥ 65 years, N 5 396) and 889 matched controls were selected for this analysis. Overall, prostate cancer risks were unrelated to serum T, estimated free and bioavailable T, and SHBG; however, risks increased with increasing T:SHBG ratio (p trend 5 0.01), mostly related to risk in older men (≥65 years, p trend 5 0.001), particularly for aggressive disease [highest versus lowest quartile: odds ratio (OR) 2.76, 95% confidence interval (CI) 1. 50-5.09]. No clear patterns were noted for D4-A and 3a-diolG. In summary, our large prospective study did not show convincing evidence of a relationship between serum sex hormones and prostate cancer. T:SHBG ratio was related to risk in this older population of men, but the significance of this ratio in steroidal biology is unclear. ' 2008 Wiley-Liss, Inc.Key words: prostate; hormones; testosterone; 3a-diolG; sex hormonebinding globulin; androstenedione Prostate cancer is the most commonly diagnosed nonskin cancer and the second leading cause of cancer mortality among men in the United States. 1 Age, race and family history of prostate cancer are the only well-established risk factors for this disease (reviewed in Refs. 2, 3). Androgens are important in prostate cancer; prolonged administration of testosterone induces prostate cancer in animal models 4,5 and androgens are important modifiers of disease progression and metastases. 6,7 Testosterone (T) is derived in the testes from androstenedione (D4-A) and is converted in the prostate to its more active form, dihydrotestosterone (DHT). 8 DHT binds in a complex to the androgen receptor (AR), influencing cellular proliferation through control of numerous gene-regulating AR response elements. DHT is further metabolized to 3a-androstanediol (3a-diol) and 3a-androstanediol glucuronide (3a-diolG). In circulation, sex hormone-binding globulin (SHBG) is the major high-affinity carrier of T, while serum albumin serves as an androgen carrier of low binding affinity. 8 SHBG may also play a role directly in steroid signaling, through binding to a receptor (R SHBG ), inducing cAMP synthesis (reviewed in Ref. 9).Although androgens are important in prostate carcinogenesis, 10 epidemiologic studies relating serum hormone levels to prostate cancer risk have been inconclusive, with most prospective studies in the United States an...

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“…8 SHBG may also play a role directly in steroid signaling, through binding to a receptor (R SHBG ), inducing cAMP synthesis (reviewed in Ref. 9).…”

mentioning

confidence: 99%

Endogenous sex hormones and the risk of prostate cancer: A prospective study

Weiss¹,

Huang²,

Rinaldi

et al. 2008

Intl Journal of Cancer

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“…It was originally described as a hepatically secreted protein, and it also functions as part of a novel steroid signaling system that is independent of the classical intracellular steroid receptors. Unlike the intracellular steroid receptors that are ligand-activated transcription factors, SHBG mediates androgen and estrogen signaling at the cell membrane by way of cAMP (Kahn, 2003). SHBG may be important both physiologically and in a number of endocrine disorders including PCOS (Anderson, 1974).…”

Section: Pcos Laboratory and Sonographic Evaluationmentioning

confidence: 99%

Menstrual Cycle Disturbances at Reproductive Age

Skałba¹

2011

Update on Mechanisms of Hormone Action - Focus on Metabolism, Growth and Reproduction

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“…[10][11][12] Sex hormone binding globulin (SHBG) is a plasma glycoprotein synthesized by hepatocytes and also produced by the Sertoli cells. 13,14 SHBG regulate androgen action and reversible with high affinity to androgens in circulation (DHT, testosterone, 3α-androstenediol) and estrogen with lower affinity. 13,15 In older men, increased of SHBG levels followed by decreased of FT levels, but TT levels did not change.…”

Section: Introductionmentioning

confidence: 99%

The negative correlation between testosterone levels and age in healthy Indonesian men residing in the special capital province of Jakarta, Indonesia

Parwanto¹

2017

Int J Res Med Sci

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Background: Testosterone levels in the circulation determined by production and secretion by Leydig cell in the testes. The action mechanism of testosterone to target cells mediated by sex hormone binding globulin (SHBG). The levels of testosterone and SHBG in circulation determine men's health. The objective in this study to know the relationship between testosterone, SHBG and insulin with age in healthy Indonesian men residing in the special capital province of Jakarta, Indonesia.Methods: This study is a cross-sectional study involving 250 healthy Indonesian men residing in the special capital province of Jakarta, Indonesia. Consecutive sampling was done in this study. Testosterone, SHBG and insulin in the serum were measured by immunoradiometric assay (IRMA). Glucose, triglycerides and albumin were measured using a spectrophotometer. Regression analysis was done to know the correlation between testosterone, SHBG and insulin with age.Results: The levels of TT, free testosterone (FT), SHBG and percentage of free testosterone (%FT) in healthy Indonesian men were negatively correlated with age (p<0.05). Free testosterone index (FTI) and insulin are not correlated with age (p>0.05). The levels of SHBG, FT, %FT and FTI were correlated positively with TT (p<0.05), but insulin did not correlate with TT (p>0.05). The %FT and FTI were positively correlated with FT (p<0.05), but SHBG and insulin levels did not correlate with FT (p>0.05). SHBG levels are not correlated with insulin (p>0.05). The rate of decline in TT levels in this study 9.8% per decade, while in SHBG levels 8.19% per decade.Conclusions: The levels of TT, FT, % FT and SHBG in this study were negatively correlated with age, but the FTI and insulin did not correlate with age. The rate of decline in TT levels in this study 9.8% per decade, while in SHBG levels 8.19% per decade.

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Sex hormone-binding globulin is synthesized in target cells

Cited by 186 publications

References 15 publications

Endogenous sex hormones and the risk of prostate cancer: A prospective study

Endogenous sex hormones and the risk of prostate cancer: A prospective study

Menstrual Cycle Disturbances at Reproductive Age

The negative correlation between testosterone levels and age in healthy Indonesian men residing in the special capital province of Jakarta, Indonesia

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